1. Field of the Invention:
The invention involves a method for the resolution of a racemic mixture of D,L-alpha-phenethylamine. Specifically, a method of resolving the racemic mixture with optically active mandelic acid provides for high yield recovery of D(+)phenethylamine with high enantiomeric purity.
2. Background of the Prior Art:
D(+)alpha-phenethylamine is a valuable intermediate in the manufacture of various pharmaceuticals. For instance, various anti-atherosclerosis agents may be prepared from fatty acid amides derived from this useful intermediate. See U.S. Pat. No. 3,980,698, Suzuki. However, given the impact of optical activity on bioavailability and pharmaceutical effectiveness, it is necessary to isolate the optical species from their racemates in high enantiomeric purity.
A wide variety of processes are known which use optically active acids in the resolution of this important intermediate. Thus, U.S. Pat. No. 2,276,508 is directed to the use of optically active tartaric acid. This patent requires several repeated and ordered crystallization steps, and does not provide for the recovery of the tartaric acid. In particular, this process requires enantiomeric purification of a solution, which may be quite difficult and expensive.
U.S. Pat. No. 4,129,580 describes the need to provide a resolving agent which can be used on a commercial scale, can be economically regenerated, and can be reused. Lasalocid (a polyether antibiotic) is identified as such an agent, but remains largely commercially unsatisfactory for the resolution of D,L-alpha-phenethylamine. One problem common to this and tartaric acid processes is the need to use large molar equivalents of the resolving agent.
U.S. Pat. No. 3,980,098 identifies a number of potential resolution agents for alkylphenyl ethylamines including optically active mandelic acid, but directs those of skill in the art away from such use due to the cost and lack of recovery of the resolving agent and difficulties encountered in purification. Column 1, lines 60-68.
In a similar process, D,L-phenylalanine is resolved with optically active mandelic acid in the presence of a stabilizing acid. U.S. Pat. No. 4,582,928. This patent uses the L-mandelic acid to recover the L-isomer desired, and does not provide for recovery of the resolving agent.
Accordingly, it remains an object of the art to provide a process for the resolution of D,L-alpha-phenethylamine that requires limited amounts of a recoverable resolving agents, while providing high yields and high enantiomeric purity.